Tobacco Dependence
Conditions
Brief summary
Schizophrenia is associated with high rates of cigarette smoking and associated morbidity and mortality. In this study, smokers with schizophrenia will complete a baseline session and then randomized to varenicline (VAR) or placebo (PLA). After 1 week on medication, participants will complete a cigarette rating task session. Participants will then undergo a 72-hr abstinence period in which they will come to the laboratory twice per day and receive high-value cash reinforcement contingent upon meeting a strict breath CO abstinence criterion. At each visit, they will rate withdrawal symptoms, mood and craving. At the end of the abstinence period, they will repeat the cigarette rating task. Participants will return to the lab to provide a CO sample 24 hours later, and will text the lab with videos of their CO samples for one week. Date and time of smoking relapse will be measured from these samples.
Interventions
DRUGVarenicline
Standard dosing: 0.5 mg/day on days 1-3, 0.5 mg twice daily (morning, evening) on days 4-7, then 1 mg twice daily to the end of the medication period.
DRUGPlacebo
Dosing schedule matched to active comparator: on tablet on days 1-3, one tablet twice daily (morning, evening) on days 4-7, then one tablet twice daily to the end of the medication period.
Sponsors
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women 2. Ages 18-65 3. Have schizophrenia or schizoaffective disorder 4. Would like to quit smoking within the next 6 months 5. Have smoked at least 10 cigarettes per day in the past year 6. Have breath CO level \> 10 ppm 7. Able to speak, read and comprehend English well enough to complete study procedures
Exclusion criteria
1. Pregnant, breast-feeding, or unwilling to use medically-approved contraception 2. Currently using varenicline, bupropion or nicotine replacement therapy for smoking cessation 3. Medical disease that would preclude participation 4. Unstable psychiatric conditions 5. Body mass index (BMI) \< 15 or \> 38 kg/m2 6. Past-month suicidal intention, with or without a specific plan 7. Positive urine drug screen or breath alcohol level \> 0.01% at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Questionnaire on Smoking Urges - Brief Form | 72 hrs abstinence | Average of all items, rated from 1 (strongly disagree) to 7 (strongly agree). Higher scores indicate higher levels of smoking urge or craving. |
| Minnesota Nicotine Withdrawal Scale - Negative Affect Scale | 72 hrs abstinence | Average of responses to the anger, depression, anxiety and difficulty concentrating items, which are rated from 0 (not present) to 4 (severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Cigarette Evaluation Questionnaire - Satisfaction Scale | 72 hrs abstinence | Average of the satisfaction, taste and enjoyment items, which are rated from 1 (not at all) to 7 (extremely) |
| Modified Cigarette Evaluation Questionnaire - Reward Scale | 72 hrs abstinence | Average of the calm, feel more awake, less irritable, help to concentrate and reduce hunger items, which are rated from 1 (not at all) to 7 (extremely) |
| Latency to Smoking Relapse | 1 week | hours until relapse during a smoking abstinence period, verified with breath carbon monoxide (CO) levels |
Other
| Measure | Time frame | Description |
|---|---|---|
| Brief Psychiatric Rating Scale | 72 hrs abstinence | Sum of all items rated from 1 (not present) to 7 (extremely severe) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Varenicline: Standard dosing: 0.5 mg/day on days 1-3, 0.5 mg twice daily (morning, evening) on days 4-7, then 1 mg twice daily to the end of the medication period. | 3 |
| Placebo Placebo: Dosing schedule matched to active comparator: on tablet on days 1-3, one tablet twice daily (morning, evening) on days 4-7, then one tablet twice daily to the end of the medication period. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Unable to meet smoking abstinence criterion | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Varenicline | Placebo |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 7.9 | 52.7 years STANDARD_DEVIATION 8.5 | 46 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fagerstrom Test of Nicotine Dependence score | 7.6 units on a scale STANDARD_DEVIATION 1.8 | 8.3 units on a scale STANDARD_DEVIATION 2.1 | 6.5 units on a scale STANDARD_DEVIATION 0.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 1 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 1 / 2 |
Outcome results
Primary
Minnesota Nicotine Withdrawal Scale - Negative Affect Scale
Average of responses to the anger, depression, anxiety and difficulty concentrating items, which are rated from 0 (not present) to 4 (severe).
Time frame: 72 hrs abstinence
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Minnesota Nicotine Withdrawal Scale - Negative Affect Scale | 1.45 score on a scale | Standard Deviation 0.57 |
| Placebo | Minnesota Nicotine Withdrawal Scale - Negative Affect Scale | 0.85 score on a scale | Standard Deviation 0.92 |
Primary
Questionnaire on Smoking Urges - Brief Form
Average of all items, rated from 1 (strongly disagree) to 7 (strongly agree). Higher scores indicate higher levels of smoking urge or craving.
Time frame: 72 hrs abstinence
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Questionnaire on Smoking Urges - Brief Form | 3.12 score on a scale | Standard Deviation 2.11 |
| Placebo | Questionnaire on Smoking Urges - Brief Form | 4.41 score on a scale | Standard Deviation 2.72 |
Secondary
Latency to Smoking Relapse
hours until relapse during a smoking abstinence period, verified with breath carbon monoxide (CO) levels
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Latency to Smoking Relapse | 8 hours | Standard Deviation 0 |
| Placebo | Latency to Smoking Relapse | 24 hours | Standard Deviation 0 |
Secondary
Modified Cigarette Evaluation Questionnaire - Reward Scale
Average of the calm, feel more awake, less irritable, help to concentrate and reduce hunger items, which are rated from 1 (not at all) to 7 (extremely)
Time frame: 72 hrs abstinence
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Modified Cigarette Evaluation Questionnaire - Reward Scale | 4.00 score on a scale | Standard Deviation 0.35 |
| Placebo | Modified Cigarette Evaluation Questionnaire - Reward Scale | 4.30 score on a scale | Standard Deviation 0 |
Secondary
Modified Cigarette Evaluation Questionnaire - Satisfaction Scale
Average of the satisfaction, taste and enjoyment items, which are rated from 1 (not at all) to 7 (extremely)
Time frame: 72 hrs abstinence
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Modified Cigarette Evaluation Questionnaire - Satisfaction Scale | 5.33 score on a scale | Standard Deviation 1.15 |
| Placebo | Modified Cigarette Evaluation Questionnaire - Satisfaction Scale | 3.43 score on a scale | Standard Deviation 1.2 |
Other Pre-specified
Brief Psychiatric Rating Scale
Sum of all items rated from 1 (not present) to 7 (extremely severe)
Time frame: 72 hrs abstinence
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Brief Psychiatric Rating Scale | 1.33 score on a scale | Standard Deviation 0.11 |
| Placebo | Brief Psychiatric Rating Scale | 1.37 score on a scale | Standard Deviation 0.06 |